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Inhibition of Collagenase Q1 of Bacillus cereus as a Novel Antivirulence Strategy for the Treatment of Skin-Wound Infections

  • Abstract Despite the progress in surgical techniques and antibiotic prophylaxis, opportunistic wound infections with Bacillus cereus remain a public health problem. Secreted toxins are one of the main factors contributing to B. cereus pathogenicity. A promising strategy to treat such infections is to target these toxins and not the bacteria. Although the exoenzymes produced by B. cereus are thoroughly investigated, little is known about the role of B. cereus collagenases in wound infections. In this report, the collagenolytic activity of secreted collagenases (Col) is characterized in the B. cereus culture supernatant (csn) and its isolated recombinantly produced ColQ1 is characterized. The data reveals that ColQ1 causes damage on dermal collagen (COL). This results in gaps in the tissue, which might facilitate the spread of bacteria. The importance of B. cereus collagenases is also demonstrated in disease promotion using two inhibitors. Compound 2 shows high efficacy in peptidolytic, gelatinolytic, and COL degradation assays. It also preserves the fibrillar COLs in skin tissue challenged with ColQ1, as well as the viability of skin cells treated with B. cereus csn. A Galleria mellonella model highlights the significance of collagenase inhibition in vivo.

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Document Type:Article
Author:Alaa AlhayekORCiD, Essak S. KhanORCiD, Esther SchönauerORCiD, Tobias DäinghausORCiD, Roya Shafiei, Katrin VoosORCiD, Mitchell K. L. Han, Christian DuchoORCiD, Gernot PosseltORCiD, Silja WesslerORCiD, Hans BrandstetterORCiD, Jörg HaupenthalORCiD, Aránzazu del Campo BécaresORCiD, Anna Katharina H. HirschORCiD
Parent Title (English):Advanced therapeutics
First Page:2100222
Year of first Publication:2022
Release Date:2022/05/05
Tag:Bacillus cereus; antibiotic resistance; collagenase; pathoblocker; virulence factors
Impact:04.600 (2022)
Funding Information:Helmholtz-Zentrum für Infektionsforschung GmbH, European Research Council (ERC starting grant 757913), and Austrian Science Fund (P 31843 and I 4360)
Scientific Units:Dynamical Biomaterials
DDC classes:500 Naturwissenschaften und Mathematik / 570 Biowissenschaften, Biologie
Open Access:Open Access
Signature:INM 2022/020
Licence (German):License LogoCreative Commons - CC BY - Namensnennung 4.0 International